Search Results (62)

Background: The gut microbiome might be affected by proton-pump inhibitors (PPIs), increasing the risk of Clostridioides difficile infection (CDI); however, the association between PPIs and Clostridioides difficile infection (CDI) remains controversial. Aim: The aim of this study is to reevaluate the association between PPIs and CDI based on pharmacovigilance data, taking competition bias into account. Methods: PPI-related CDI adverse event reports, based on the Food and Drug Administration adverse event reporting system database from 2004 to 2023, were analyzed. Included PPI cases were stratified into CDI and non-CDI groups. Disproportionality analysis was performed using the reporting odds ratio (ROR) and information component (IC). The effect of competition bias on signal detection was quantitatively investigated. Age-stratified analyses were conducted to assess residual confounding. Results: A total of 238,470 PPI reports were included, with 1268 cases in the CDI group and 237,202 cases in the non-CDI group. Initial analysis revealed a significant PPI-CDI association (ROR = 2.36, 95% confidence interval (95%CI) 2.19 to 2.53; IC = 1.21, 95%CI 0.97 to 1.45), with CDI signals detected for five PPI agents, including pantoprazole, omeprazole, lansoprazole, rabeprazole, and dexlansoprazole. After excluding competition from antibacterial drugs, CDI signal strength decreased substantially (ROR = 1.47, 95%CI 1.34 to 1.62; IC = 0.55, 95%CI 0.23 to 0.87), retaining a significant CDI signal only for rabeprazole and pantoprazole. Upon further exclusion of antibacterial or immunosuppressive drug users and renal injury event cases, CDI signal strength decreased (ROR = 1.48, 95%CI 1.32 to 1.66; IC = 0.56, 95%CI 0.18 to 0.94), with pantoprazole as the sole CDI signal drug. Age-stratified analyses demonstrated complete signal loss after antibacterial drug adjustment across all age groups. Conclusions: The current large-scale pharmacovigilance study indicated that the observed PPI-CDI association may be mediated predominantly by antibacterial drug co-exposure rather than PPI direct causation. Full article

Background: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of advanced liver disease, driven primarily by ammonia accumulation due to impaired hepatic detoxification and portosystemic shunting. Lactulose is a cornerstone therapy, while rifaximin serves as an effective adjunct for reducing recurrence and hospitalizations. Methods: We conducted a retrospective cohort study at Constanța Emergency County Hospital from January 2022 to March 2025, including 120 adult patients diagnosed with HE. Inclusion criteria were confirmed diagnosis of cirrhosis with clinical and/or biochemical evidence of HE. Patients with other primary neurological disorders or incomplete medical records were excluded. Data on demographics, comorbidities, laboratory results, and medications were collected. Statistical analyses were performed employing descriptive statistics, Friedman’s two-way ANOVA by ranks for medication use, and Cox proportional hazards regression to assess survival associations. Results: The mean age was 61.19 years, with high prevalence of anemia (mean hemoglobin: 9.35 g/dL) and thrombocytopenia (mean: 121.86 × 10³/µL). Inflammatory markers were elevated (mean CRP: 36.95 mg/L; ESR: 55.83 mm/h), and INR averaged 1.86. Lactulose was administered to 63.3% of patients, rifaximin to 52.5%, with diuretics, pantoprazole, and albumin being frequently used. Friedman’s analysis ranked lactulose highest in usage frequency. Cox regression indicated no significant short-term survival difference associated with toxic encephalopathy or rifaximin use. Conclusion: In this cohort, lactulose remained the primary treatment for HE, often complemented by supportive pharmacotherapy. While rifaximin use was limited, the overall medication patterns reflected standard practice priorities in HE management. Full article

Background: Metformin and proton pump inhibitors (PPIs) are independently associated with vitamin B12 deficiency. Despite frequent co-prescription, particularly in diabetics with gastroesophageal disorders, evidence regarding the combined risk of these medications on vitamin B12 deficiency remains limited. This study aimed to evaluate the real-world risk of vitamin B12 deficiency associated with metformin, PPIs, and their combinations using the United States Food and Drug Administration Adverse Event Reporting System (USFDA AERS) database. Methods: We conducted a disproportionality analysis using USFDA AERS data from 2004 to 2024. We assessed whether metformin, PPIs, or their combinations were reported more often than expected with vitamin B12 deficiency and evaluated associated clinical outcomes, such as hospitalization and life-threatening events. Results: Among 29,661,136 reports, 552 met inclusion criteria, with metformin monotherapy accounting for 274 cases. Positive safety signals were detected for both metformin and all PPIs individually. While statistical interaction measures were not conclusive, patients on metformin–pantoprazole combination therapy experienced significantly higher rates of hospitalization and life-threatening events compared to those on pantoprazole alone. Conclusions: These findings suggest that patients receiving metformin and PPIs together, particularly the elderly, may face a higher risk of serious vitamin B12 deficiency-related complications. Clinicians should consider closer monitoring of vitamin B12 levels and supplementation when needed in patients on combination therapy. Full article

Cancer cells can adapt to their surrounding microenvironment by upregulating glucose-regulated protein 78 kDa (GRP78) and vacuolar-type ATPase (V-ATPase) proteins to increase their proliferation and resilience to anticancer therapy. Therefore, targeting these proteins can obstruct cancer progression. A comprehensive computational study was conducted to investigate the inhibitory potential of four proton pump inhibitors (PPIs), dexlasnoprazole (DEX), esomeprazole (ESO), pantoprazole (PAN), and rabeprazole (RAB), against GRP78 and V-ATPase. Molecular docking revealed high-affinity scores for PPIs against both proteins. Moreover, molecular dynamics showed favorable root mean square deviation values for GRP78 and V-ATPase complexes, whereas root mean square fluctuations were high at the substrate-binding subdomains of GRP78 complexes and the α-helices of V-ATPase. Meanwhile, the radius of gyration and the surface-accessible surface area of the complexes were not significantly affected by ligand binding. Trajectory projections of the first two principal components showed similar motions of GRP78 structures and the fluctuating nature of V-ATPase structures, while the free-energy landscape revealed the thermodynamically favored GRP78-RAB and V-ATPase-DEX conformations. Furthermore, the binding free energy was −16.59 and −18.97 kcal/mol for GRP78-RAB and V-ATPase-DEX, respectively, indicating their stability. According to our findings, RAB and DEX are promising candidates for GRP78 and V-ATPase inhibition experiments, respectively. Full article

Background/Objectives: Potassium-competitive acid blockers (P-CABs) offer rapid gastric acid inhibition and lower toxicity compared to proton pump inhibitors (PPIs). This study investigates the drug–drug interaction between P-CABs and immunosuppressants tacrolimus and mycophenolate in kidney transplant recipients (KTRs). Methods: Sixty-two KTRs were randomized to receive either 50 mg of tegoprazan or 20 mg of pantoprazole. Patients were monitored using a smart clinical trial platform incorporating remote monitoring and safety management systems, which tracked drug adherence and vital signs. General and gastrointestinal (GI) symptoms were surveyed via a self-developed app on patients’ phones. Trough levels of tacrolimus and mycophenolate were measured every 4 weeks over 12 weeks. Results: Medication adherence was 100% in both groups. A total of 13,726 biometric data points and 5031 questionnaire responses were collected, with 5704 feedback messages and 56 video visits conducted. At 12 weeks, the mean trough levels of tacrolimus and mycophenolate were similar between the tegoprazan and pantoprazole groups (5.5 ± 1.6 vs. 5.8 ± 2.0 ng/mL, p = 0.50 and 2.7 ± 1.4 vs. 2.6 ± 1.4 µg/mL, p = 0.57, respectively). The intragroup difference in trough levels from baseline to week 12 was not significant in either group. GI symptoms scores, vital signs, and allograft function remained stable and comparable between groups. Conclusions: Tegoprazan does not alter the blood trough levels of tacrolimus and mycophenolate during the 12-week follow-up in KTRs and has a similar impact on GI symptoms as pantoprazole. This study confirms the feasibility and safety of using a smart clinical trial system with remote monitoring for randomized trials. Full article

Background: The efflux system is one of the resistance mechanisms that bacteria use to reduce the effectiveness of antibiotics, leading to the development of multidrug resistance. To evaluate other treatment choices, esomeprazole (ESO), omeprazole (OME), pantoprazole (PAN), vitamin D (VD), and vitamin K (VK) were tested for potential efflux pump (EP)-inhibiting activity. Methods: The minimum inhibitory concentrations (MICs) of the tested drugs were determined against K. pneumoniae ATCC 51503 and P. aeruginosa PAO1. Quantitative estimation of the EP-inhibiting activity of the tested medications was phenotypically investigated with a semi-automated fluorometric system and genotypically confirmed by real-time polymerase chain reaction (RT-PCR). Data were confirmed through docking study. Results: K. pneumoniae ATCC 51503 and P. aeruginosa PAO1 were positive efflux standard strains. VD and VK revealed an MIC_VD of 625–1250 µg/mL and MIC_VK of 2500–5000 µg/mL, lower than what was detected for PPIs (MIC_PPIs = 16,000–32,000 µg/mL). Vitamins showed powerful anti-efflux activity with remarkable ethidium bromide accumulation in K. pneumoniae ATCC 51503 and P. aeruginosa PAO1. Also, VD and VK significantly lowered the MIC of ciprofloxacin by 64-fold. On the molecular level, OME showed a notable decrease in the relative expression of the efflux-encoding genes acrB and mexA by 91.5% and 99.7% in ATCC 51503 and PAO1, respectively. Conclusion: This study highlights the anti-efflux activity of ESO, OME, PAN, VD, and VK against the tested Gram-negative strains. Hence, these PPIs and vitamins could be valuable adjuvant treatments to enhance the effectiveness of curing infections caused by MDR strains. Full article

Background: Proton pump inhibitors (PPIs) are widely used for gastric acid suppression, yet their efficacy and safety in neonates and infants remain unclear. While esomeprazole is the only Food and Drug Administration (FDA)-approved PPI for neonates and infants under 1 year of age, other PPIs are also frequently prescribed. Objectives: This study utilizes FDA Adverse Event Reporting System (FAERS) data to evaluate potential adverse drug events (ADEs) of PPIs, providing crucial real-world insights into their safety in this vulnerable population. Methods: This observational cross-sectional study was conducted using an individual case safety report (ICSR) database. Only reports in neonates or infants receiving omeprazole, pantoprazole, lansoprazole, rabeprazole, or esomeprazole monotherapy were evaluated. The most frequently prescribed PPI, the most common indication, the most reported ADE, the seriousness of AEs, and the countries reporting the highest ADE number were analyzed using 2D disproportionality analyses (e.g., reporting odds ratio (RORs)). Results: A total of 464 patients were included; 323 (69.6%) of them were stated as serious and 15 (3.2%) of them were stated as time-related to mortality. Most of the ADEs were reported for lansoprazole (45.9%). The most reported PPI-associated ADE was vomiting (8.8%). According to the RORs analysis, vomiting associated with PPI monotherapy was more likely to occur (RORs: 2.88, 95% CI: 2.09–3.96), which is followed by diarrhea, hypertrichosis, choking, and erythema. Additionally, medication errors were reported in 50 (10.8%) patients. Conclusions: ICSR databases are valuable pharmacovigilance tools. The absence of access to a causality assessment is a limitation since it limits its ability to confirm whether the ADEs are truly caused by the suspected drug, mitigated using RORs analysis. Integrating neonatal-specific algorithms could enhance drug safety evaluations, strengthen evidence-based decision-making, and improve risk–benefit assessments in neonates and infants. Full article

Background/Objectives: Rhabdomyolysis, a dangerous breakdown of skeletal muscle, has been reported as an adverse event in those prescribed a statin therapy for the treatment of hypercholesterolemia. Statin drugs are some of the most prescribed treatments for elevated cholesterol levels. The purpose of this comparative study was to determine the association between the statin drugs used and the risk of rhabdomyolysis using the FDA Adverse Event Reporting System (FAERS) and transcriptomic data. Methods: A disproportionality analysis was performed to compare the risk of rhabdomyolysis between the reference statin drug (simvastatin) and the treatment group, with patient age assessed as a possible confounder. In addition, association rule mining was utilized to both identify other adverse events that frequently presented with rhabdomyolysis and identify possible drug-drug interactions (DDIs). Finally, public transcriptomic data were explored to identify the possible genetic underpinnings highlighting these differences in rhabdomyolysis risk across statins. Results: Rhabdomyolysis is a commonly reported adverse event for patients treated with statins, particularly those prescribed simvastatin. Simvastatin was associated with a more than 2-fold increased likelihood of rhabdomyolysis compared to other statins. Men were twice as likely to report rhabdomyolysis than women regardless of statin treatment, with the highest risk observed for pravastatin (ROR = 2.30, p < 0.001) and atorvastatin (ROR = 2.03, p < 0.0001). Several possible DDIs were identified, including furosemide/Lasix, allopurinol clopidogrel/Plavix, and pantoprazole, which may elevate rhabdomyolysis risk through impaired muscle function and delayed statin metabolism. Finally, nine myopathic genes were identified as possible regulators of statin-induced rhabdomyolysis, including DYSF, DES, PLEC, CAPN3, SCN4A, TNNT1, SDHA, MYH7, and PYGM in primary human muscle cells. Conclusions: Simvastatin was associated with the highest risk of rhabdomyolysis. The risk of rhabdomyolysis was more pronounced in men than women. Several possible DDIs were identified including furosemide/Lasix, allopurinol clopidogrel/Plavix, and pantoprazole. Full article

Green chemistry principles are pivotal in driving sustainable and innovative solutions to global health challenges. This study explores a hydroalcoholic extract from Castanea sativa (chestnut) burrs, an underutilized natural resource, as a potent source of antimicrobial compounds against Helicobacter pylori (H. pylori). The extract demonstrated significant bactericidal activity, synergizing effectively with clarithromycin and showing additive effects with metronidazole. Remarkably, combining the extract with clarithromycin and sub-inhibitory concentrations of pantoprazole reduced clarithromycin’s Minimum Bactericidal Concentration (MBC) to just 1.56% of its original value. Mechanistic studies suggest that the extract’s polyphenolic compounds compromise bacterial membrane integrity, enhancing antibiotic uptake, while pantoprazole disrupts bacterial ATPase activity. This research highlights the critical role of natural product extraction within the framework of green chemistry, offering a sustainable and environmentally friendly alternative to synthetic antimicrobials. By harnessing bioactive compounds from plant sources, this approach addresses the pressing issue of antibiotic resistance while promoting the responsible use of natural resources. The findings underscore the transformative potential of green chemistry in developing effective, eco-conscious antimicrobial therapies that align with global sustainability goals. Full article

Novel direct oral anticoagulants (DOACs) are prescribed worldwide in the treatment of non-valvular atrial fibrillation. Adverse reactions have been reported following the use of DOACs. One notable trend in the literature is the growing number of reported cases of esophagitis dissecans superficialis (EDS) generated by DOAC use. We hereby report the case of a 73-year-old woman who presented to the hospital with asthenia, dysphagia, and melena two days prior to admission. The patient had taken apixaban due to non-valvular paroxysmal atrial fibrillation for a few weeks. The biological panel showed moderate anemia with a hemoglobin level of 7.7 g/dL Apixaban-induced EDS was diagnosed by the characteristic endoscopic findings. The patient received treatment with a proton pump inhibitor (pantoprazole) in a double dose. Also, an iron treatment was recommended for a period of six months. The follow-up endoscopy at one month confirmed the healing of the esophageal lesions. The case was discussed with the cardiologist. The first anticoagulant treatment proposed after discharge was a vitamin K antagonist (acenocumarol) but the patient refused this medication and thus it was decided to initiate rivaroxaban. Although DOACs have demonstrated their efficacy in the prevention and treatment of stroke and thromboembolism among the aging demographic, cases of DOAC-induced EDS will continue to pose numerous challenges for physicians worldwide. Full article

Achieving clinical effectiveness with vitamin K antagonists (VKAs) requires a Time in Therapeutic Range (TTR) above 65%. TTR is influenced by genetics (CYP2C9, VKORC1, CYP4F2), treatment adherence, and knowledge. The SAMe-TT2R2 algorithm is used to assess VKA treatment suitability. In this case report, SAMe-TT2R2 and pharmacogenetic analysis were used to improve oral anticoagulant management in a patient with poor control of INR. An 84-year-old, obese male with atrial fibrillation, undergoing acenocoumarol therapy, had a suboptimal TTR. An assessment with the SAMe-TT2R2 algorithm indicated a favorable profile for VKA use. An educational intervention on vitamin K-rich foods was conducted, and his physician was informed about the interaction between omeprazole and acenocoumarol, recommending its replacement with pantoprazole. This intervention was accepted by the physician and, three months post-intervention, the patient’s TTR improved to 100%. Poor adherence and limited knowledge contributed to treatment failures in patients with a good VKA profile. Pharmaceutical interventions significantly improved TTR management. Patients with favorable genetic and clinical profiles could achieve adequate control of their anticoagulant medication through these interventions. Predictive tools may help select patients who can effectively and safely use VKAs through pharmaceutical interventions. Full article

Introduction: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis. Methods: We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs). Results: Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16–1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13–1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes. Conclusions: Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations. Full article

Objectives: To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on maintenance hemodialysis. Methods: Patients were defined as experiencing PDF if they spontaneously offered this complaint when asked the open-ended question: “Do you feel fatigued after dialysis?”. Time of recovery after dialysis (TIRD) was also assessed for each patient. Each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. We defined if patients used PPI (no PPI use or PPI use), the type of used PPI, the dose of used PPI, and the duration of the use of PPI (<1 year or ≥1 year). Results: A total of 346 patients were studied: 259 used PPI (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Two hundred and thirty-two patients declared PDF and 114 did not. The median [min–max] TIRD was 210 min [0–1440]. The prevalence of PDF in PPI users and PPI non-users was 67% and 68%, respectively (p = 0.878). The median [min–max] TIRD did not differ significantly between PPI users and PPI non-users (180 [0–1440] and 240 [0–1440], respectively; p = 0.871). Median PDF intensity, duration, frequency, and severity did not differ significantly between PPI use and no use. The prevalence of PDF was similar among the different types of PPI use and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 40 patients and ≥1 year in 219 patients. The prevalence of PDF did not differ between the two exposures. The correlation matrix between PPI equivalent dose, PPI treatment duration and PDF frequency, PDF characteristics, and TIRD showed whether there was statistical significance. Conclusions: The use of PPI is not associated with PDF and time of recovery after dialysis in patients on maintenance hemodialysis. Full article

Liver transplant patients are frail subjects due to lifelong therapy with immunosuppressants. In these patients, comorbidity and polytherapy increase the risk of adverse drug reactions. In this study, we report the development of hyponatremia, probably related to pantoprazole in a liver transplant patient. Sertraline dismission and treatment with sodium chloride did not improve clinical symptoms and laboratory levels. Pantoprazole dismission induced an improvement in clinical symptoms and the normalization of sodium levels. A five-month follow-up revealed the absence of clinical symptoms and normal serum sodium levels. Full article

Concomitant therapy (CT) and bismuth quadruple therapy (BQT) are recommended in geographical areas with high clarithromycin resistance for Helicobacter pylori (H. pylori) eradication. We compared CT and BQT as the first lines of treatment in a randomized controlled trial. Consecutive patients with H. pylori diagnosed by concordance of both a urea breath test and histology were recruited. For BQT, patients received 3 Pylera^TM capsules q.i.d.; for CT, 1000 mg of amoxicillin b.i.d, 500 mg of clarithromycin b.i.d and 500 mg of metronidazole b.i.d. As a proton pump inhibitor, 40 mg of pantoprazole b.i.d was administered. Both regimens lasted 10 days. In total, 46 patients received CT and 38 BQT. Both groups were comparable for age (p = 0.27) and sex (p = 0.36). We did not record any drop outs; therefore, the intention to treat and per protocol rates coincided. The most common symptoms were heartburn and post-prandial fullness, which were equally present in both groups. The success rate was 95.6% for CT and 100% for BQT (p = 0.56). Side effects were recorded in 23.9% and 31.6% of patients in the CT and BQT arms, respectively (p = 0.47). The most common ones were abdominal pain (8) and diarrhea (6). In conclusion, CT and BQT are equally effective in our area with high clarithromycin resistance, southern Italy, and showed comparable safety. Full article